In vitro and in vivo comparison of eravacycline- and tigecycline-based combination therapies for tigecycline-resistant Acinetobacter baumannii

Abstract

Several antimicrobial combination therapies are used to treat multiple drug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii infections. A novel antibiotic, eravacycline, shows a higher potency than tigecycline. The efficacies of eravacycline-based therapies have not yet been evaluated. We demonstrated the effectiveness of eravacycline- and tigecycline-based combination therapies in XDR and especially tigecycline resistant A. baumannii. Thirteen eligible isolates were selected from 642 non-duplicate Acinetobacter blood isolates from four medical centres in 2010–2014. Tigecycline/imipenem and eravacycline/imipenem combinations were simultaneously effective against some isolates in vitro with fractional inhibitory concentration index of 0.5. In contrast, eravacycline- and tigecycline-based combination therapies provided no additional benefits in mouse survival compared to those for monotherapy. In summary, colistin is still the final resort for XDR-A. baumannii treatment according to the sensitivities. Owning to rapid development of resistance in A. baumannii, novel antibiotics are urgently needed.

Keywords:

• Eravacycline
• tigecycline
• combination
• Acinetobacter
• synergy
• colistin
• polymyxin

Acknowledgments

The members of the ACTION study group include Te-Li Chen (Graduate Institute of Life Sciences, National Defense Medical Center), Yuag-Meng Liu (Changhua Christian Hospital), Po-Liang Lu (Kaoshiung Medical University Hospital), Chang-Pan Liu (Mackay Memorial Hospital), Ya-Sung Yang (Tri-Service General Hospital of the National Defense Medical Center), Shu-Chen Kuo (National Institute of Infectious Diseases and Vaccinology of the National Health Research Institute), Aristine Cheng (National Taiwan University Hospital), Yea-Yuan Chang (National Yang-Ming University Hospital and Taipei City Hospital, Renai Branch), and Yi-Tzu Lee (Taipei Veterans General Hospital).

Disclosure statement

All authors declare that they have no competing interests.

Additional information

Funding

This work was supported by Tri-Service General Hospital (TSGH-C107-098, TSGH-C108-137, TSGH-C109-144 and TSGH-E-110204), and the Ministry of Science and Technology (MOST 107-2314-B-075-066-MY3, MOST 107-2314-B-016-051-MY3, and MOST 108-2314-B-016-029 and MOST 110-2314-B-016-062).